Ischemia detection using intra-cardiac signals

ABSTRACT

An implanted cardiac rhythm management device is disclosed that is operative to detect myocardial ischemia. This is done by evaluating electrogram features to detect an electrocardiographic change; specifically, changes in electrogram segment during the early part of an ST segment. The early part of the ST segment is chosen to avoid the T-wave.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.11/130,858, filed May 16, 2005, which claims the benefit of U.S.Provisional Application Ser. No. 60/572,312, filed May 17, 2004.

FIELD OF THE INVENTION

This invention relates to implanted medical devices and, moreparticularly, to implanted medical devices that are capable of detectingmyocardial ischemia.

BACKGROUND

Myocardial ischemia results from insufficient blood flow to the heartmuscle. Ischemia may occur chronically, and to varying degrees, due tocoronary artery disease (CAD) or acutely due to sudden increased demand,embolism or vasospasm. Ischemia can lead to angina and eventually tomyocardial infarction—permanent damage to the heart muscle. Moreover,both ischemia and infarction can trigger fatal arrhythmias.

Ischemia can be detected by electrocardiographic changes. Conventionaldetection is through ST segment elevation shown in surface ECG.Detection through surface ECG is done only briefly and infrequently inthe clinic or through the use of a Holter monitor. Only those ischemicevents which happen to occur, or which may be provoked by stress testsduring monitoring are detected.

A long-term record of ischemia burden obtained through continuousmonitoring would be very useful as an adjunct to current methods ofischemia detection and diagnosis. Such a record may reveal infrequent orunprovokable ischemia perhaps associated with nascent CAD, vasospasm orembolism. Such a record could reveal trends in the progression orregression of CAD. It could also be used to gauge the efficacy of,and/or patient compliance with, a course medication.

Implantable medical devices (IMDs), such as pacemakers and implantablecardiac defibrillators (ICDs), offer the ideal platform for ischemiaburden monitoring. IMDs can constantly monitor the electrophysiologicalconditions of patients and detect the onset and/or the burden ofischemia. Prior patents such as U.S. Pat. No. 6,108,577 issued toMichael Benser or U.S. Pat. No. 6,609,023 issued to Fischell et al.describe the detection of ischemia based on ST level change detectedfrom EGMs of implanted lead electrodes.

The capability to detect ischemia may have other applications in IMDs.Because myocardial perfusion occurs during diastole, lower heart ratesare conducive to better perfusion. Therefore, an IMD should avoid pacingat high rates if ischemia is detected. An IMD may perhaps even force aventricular rate lower than the sinus rate through special pacingtechniques such as the one described in U.S. Pat. No. 6,377,852 byBornzin et al. IMDs may also alert patients of silent (asymptomatic)ischemic events so that they may take appropriate action such as takingmedication, ceasing exertion, lying down etc. IMDs may also releasethrombolytic or antithrombotic medication upon the detection ofischemia.

SUMMARY

What is described herein is a method by which an implanted cardiacrhythm management device may detect myocardial ischemia. This is done byevaluating electrogram features to detect an electrocardiographicchange; specifically, changes in electrogram segment between S and Twaves, and specifically during the early part of a ST segment. In oneembodiment, the early part of the ST segment can be the periodapproximately 50-100 milliseconds after onset of the Q-wave, or 100-150milliseconds from onset of the Q-wave, or even between 150-200milliseconds following the onset of the Q-wave.

Focusing on the early part of ST segment has an advantage in that thepotential loss of ST segment specificity for ischemia detection due to Twave modulations is reduced. T-wave morphology may be affected bynumerous metabolic, non-cardiac, and cardiac conditions other thanischemia.

Secondly, concentration on the early portion of the ST segment allowsthe ischemic detection to be performed independent of ST intervalchanges due to rate variations. In other words, the elimination of aneed to determine the time at which a T wave occurs removes potentialcomplicated methodologies that might be necessary due to wide variationsof ST intervals due to varying heart rates.

In another embodiment, the ST segment measurements are made in referenceto pre-P levels rather than a PQ interval value. It is observed that thebaseline between P and Q wave can be modulated by ischemic conditions ifthe occlusion occurs at arteries supplying blood to the atria as well asventricles. Therefore, in order to eliminate the possibility of the STadjustment being affected by drift in PQ baseline, ST segment adjustmentwill be made in reference to the pre-P level.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified diagram illustrating an exemplary implantablestimulation device in electrical communication with at least three leadsimplanted into a patient's heart and at least one other lead for sensingand/or delivering stimulation and/or shock therapy. Other devices withmore or fewer leads may also be suitable.

FIG. 2 is a functional block diagram of an exemplary implantablestimulation device illustrating basic elements that are configured toprovide cardioversion, defibrillation, pacing stimulation and/or othertissue stimulation. The implantable stimulation device is furtherconfigured to sense information and administer therapy responsive tosuch information.

FIG. 3 is a schematic of a typical IEGM signal for a patient sufferingfrom ischemia.

FIG. 4 is a graph illustrating multiple plots showing changes over timeas an episode of ischemia progresses.

FIG. 5 is a graph tracking ST segment elevation over time for an earlyportion of the ST segment and ignoring later portions of the ST segment.

FIG. 6 is a graph similar to that shown in FIG. 5 for another earlyportion of the ST segment.

FIG. 7 is a flowchart depicting an illustrative embodiment of a methodfor detecting ischemia.

FIG. 8 is a flowchart depicting one illustrative embodiment of a methodfor making ST segment measurements.

FIG. 9 is a flowchart depicting another illustrative embodiment of amethod for making ST segment measurements using ensemble averaging.

FIG. 10 is a flowchart depicting another illustrative embodiment of amethod for detecting ischemia.

DETAILED DESCRIPTION

The following description is not to be taken in a limiting sense, butrather is made merely for the purpose of describing the generalprinciples of the illustrative embodiments. The scope of the inventionshould be ascertained with reference to the issued claims. In thedescription that follows, like numerals or reference designators will beused to reference like parts or elements throughout.

Exemplary Stimulation Device

The techniques described below are intended to be implemented inconnection with any stimulation device that is configured orconfigurable to deliver cardiac therapy and/or sense information germaneto cardiac performance and/or therapy.

FIG. 1 shows an exemplary implantable medical device 100 in electricalcommunication with a patient's heart 102 by way of three leads 104, 106,108, suitable for delivering multi-chamber stimulation and shocktherapy. The leads 104, 106, 108 are optionally configurable fordelivery of stimulation pulses suitable for stimulation of nerves orother tissue. In addition, the device 100 includes a fourth lead 110having, in this implementation, three electrodes 144, 144′, 144″suitable for stimulation and/or sensing of physiologic signals. Thislead may be positioned in and/or near a patient's heart and/or remotefrom the heart.

The right atrial lead 104, as the name implies, is positioned in and/orpasses through a patient's right atrium. The right atrial lead 104optionally senses atrial cardiac signals and/or provide right atrialchamber stimulation therapy. As shown in FIG. 1, the stimulation device100 is coupled to right atrial lead 104 having, for example, an atrialtip electrode 120, which typically is implanted in the patient's rightatrial appendage. The lead 104, as shown in FIG. 1, also includes anatrial ring electrode 121. Of course, the lead 104 may have otherelectrodes as well. For example, the right atrial lead optionallyincludes a distal bifurcation having electrodes suitable for stimulationand/or sensing.

To sense atrial cardiac signals, ventricular cardiac signals and/or toprovide chamber pacing therapy, particularly on the left side of apatient's heart, the stimulation device 100 is coupled to a coronarysinus lead 106 designed for placement in the coronary sinus and/ortributary veins of the coronary sinus. Thus, the coronary sinus lead 106is optionally suitable for positioning at least one distal electrodeadjacent to the left ventricle and/or additional electrode(s) adjacentto the left atrium. In a normal heart, tributary veins of the coronarysinus include, but may not be limited to, the great cardiac vein, theleft marginal vein, the left posterior ventricular vein, the middlecardiac vein, and the small cardiac vein.

Accordingly, an exemplary coronary sinus lead 106 is optionally designedto sense atrial and ventricular cardiac activity, and to deliver leftventricular pacing therapy using, for example, at least a leftventricular tip electrode 122, left atrial pacing therapy using at leasta left atrial ring electrode 124, and shocking therapy using at least aleft atrial coil electrode 126. For a complete description of a coronarysinus lead, the reader is directed to U.S. Pat. No. 5,466,254, “CoronarySinus Lead with Atrial Sensing Capability” (Helland), which isincorporated herein by reference. The coronary sinus lead 106 furtheroptionally includes electrodes for stimulation of nerves or othertissue. Such a lead may include bifurcations or legs. For example, anexemplary coronary sinus lead includes pacing electrodes capable ofdelivering pacing pulses to a patient's left ventricle and at least oneelectrode capable of stimulating an autonomic nerve.

The stimulation device 100 is also shown in electrical communicationwith the patient's heart 102 by way of an implantable right ventricularlead 108 having, in this exemplary implementation, a right ventriculartip electrode 128, a right ventricular ring electrode 130, a rightventricular (RV) coil electrode 132, and an SVC coil electrode 134.Typically, the right ventricular lead 108 is transvenously inserted intothe heart 102 to place the right ventricular tip electrode 128 in theright ventricular apex so that the RV coil electrode 132 will bepositioned in the right ventricle and the SVC coil electrode 134 will bepositioned in the superior vena cava. Accordingly, the right ventricularlead 108 is capable of sensing or receiving cardiac signals, anddelivering stimulation in the form of pacing and shock therapy to theright ventricle. An exemplary right ventricular lead may also include atleast one electrode capable of stimulating other tissue; such anelectrode may be positioned on the lead or a bifurcation or leg of thelead.

FIG. 2 shows an exemplary, simplified block diagram depicting variouscomponents of stimulation device 100. The stimulation device 100 can becapable of treating both fast and slow arrhythmias with stimulationtherapy, including cardioversion, defibrillation, and pacingstimulation. While a particular multi-chamber device is shown, it is tobe appreciated and understood that this is done for illustrationpurposes only. Thus, the techniques, methods, etc., described below canbe implemented in connection with any suitably configured orconfigurable stimulation device. Accordingly, one of skill in the artcould readily duplicate, eliminate, or disable the appropriate circuitryin any desired combination to provide a device capable of treating theappropriate chamber(s) or regions of a patient's heart.

Housing 200 for the stimulation device 100 is often referred to as the“can”, “case” or “case electrode”, and may be programmably selected toact as the return electrode for all “unipolar” modes. Housing 200 mayfurther be used as a return electrode alone or in combination with oneor more of the coil electrodes 126, 132 and 134 for shocking or otherpurposes. Housing 200 further includes a connector (not shown) having aplurality of terminals 201, 202, 204, 206, 208, 212, 214, 216, 218, 221(shown schematically and, for convenience, the names of the electrodesto which they are connected are shown next to the terminals).

To achieve right atrial sensing, pacing and/or other stimulation, theconnector includes at least a right atrial tip terminal (A_(R) TIP) 202adapted for connection to the atrial tip electrode 120. A right atrialring terminal (A_(R) RING) 201 is also shown, which is adapted forconnection to the atrial ring electrode 121. To achieve left chambersensing, pacing, shocking, and/or autonomic stimulation, the connectorincludes at least a left ventricular tip terminal (V_(L) TIP) 204, aleft atrial ring terminal (A_(L) RING) 206, and a left atrial shockingterminal (A_(L) COIL) 208, which are adapted for connection to the leftventricular tip electrode 122, the left atrial ring electrode 124, andthe left atrial coil electrode 126, respectively. Connection to suitablestimulation electrodes is also possible via these and/or other terminals(e.g., via a stimulation terminal S ELEC 221). The terminal S ELEC 221may optionally be used for sensing.

To support right chamber sensing, pacing, shocking, and/or autonomicnerve stimulation, the connector further includes a right ventriculartip terminal (V_(R) TIP) 212, a right ventricular ring terminal (V_(R)RING) 214, a right ventricular shocking terminal (RV COIL) 216, and asuperior vena cava shocking terminal (SVC COIL) 218, which are adaptedfor connection to the right ventricular tip electrode 128, rightventricular ring electrode 130, the RV coil electrode 132, and the SVCcoil electrode 134, respectively.

At the core of the stimulation device 100 is a programmablemicrocontroller 220 that controls the various modes of cardiac detectionand/or therapy. As is well known in the art, microcontroller 220typically includes a microprocessor, or equivalent control circuitry,designed specifically for controlling the delivery of stimulationtherapy, and may further include RAM or ROM memory, logic and timingcircuitry, state machine circuitry, and I/O circuitry. Typically,microcontroller 220 includes the ability to process or monitor inputsignals (data or information) as controlled by a program code stored ina designated block of memory. The type of microcontroller is notcritical to the described implementations. Rather, any suitablemicrocontroller 220 may be used that is suitable to carry out thefunctions described herein. The use of microprocessor-based controlcircuits for performing timing and data analysis functions are wellknown in the art.

Representative types of control circuitry that may be used in connectionwith the described embodiments can include the microprocessor-basedcontrol system of U.S. Pat. No. 4,940,052 (Mann et al.), thestate-machine of U.S. Pat. No. 4,712,555 (Thornander et al.) and U.S.Pat. No. 4,944,298 (Sholder), all of which are incorporated by referenceherein. For a more detailed description of the various timing intervalsused within the stimulation device and their inter-relationship, seeU.S. Pat. No. 4,788,980 (Mann et al.), also incorporated herein byreference.

FIG. 2 also shows an atrial pulse generator 222 and a ventricular pulsegenerator 224 that generate pacing stimulation pulses for delivery bythe right atrial lead 104, the coronary sinus lead 106, and/or the rightventricular lead 108 via an electrode configuration switch 226. It isunderstood that in order to provide stimulation therapy in each of thefour chambers of the heart (or to autonomic nerves) the atrial andventricular pulse generators, 222 and 224, may include dedicated,independent pulse generators, multiplexed pulse generators, or sharedpulse generators. The pulse generators 222 and 224 are controlled by themicrocontroller 220 via appropriate control signals 228 and 230,respectively, to trigger or inhibit the stimulation pulses.

Microcontroller 220 further includes timing control circuitry 232 tocontrol the timing of the stimulation pulses (e.g., pacing rate,atrio-ventricular (AV) delay, interatrial conduction (A-A) delay, orinterventricular conduction (V-V) delay, etc.) as well as to keep trackof the timing of refractory periods, blanking intervals, noise detectionwindows, evoked response windows, alert intervals, marker channeltiming, etc., which is well known in the art.

Microcontroller 220 further includes an arrhythmia detector 234. Thedetector 234 can be utilized by the stimulation device 100 fordetermining desirable times to administer various therapies. Thedetector 234 may be implemented in hardware as part of themicrocontroller 220, or as software/firmware instructions programmedinto the device and executed on the microcontroller 220 during certainmodes of operation.

Microcontroller 220 further includes a morphology discrimination module236, a capture detection module 237, an auto sensing module 238 and anischemia detection module 239. These modules are optionally used toimplement various exemplary recognition algorithms and/or methodspresented below. The aforementioned components may be implemented inhardware as part of the microcontroller 220, or as software/firmwareinstructions programmed into the device and executed on themicrocontroller 220 during certain modes of operation. The ischemiadetection module 239, as described in greater detail below, may aid inacquisition, analysis, etc., of information relating to ischemiadetection.

The electronic configuration switch 226 includes a plurality of switchesfor connecting the desired electrodes to the appropriate I/O circuits,thereby providing complete electrode programmability. Accordingly,switch 226, in response to a control signal 242 from the microcontroller220, determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, etc.) by selectively closing the appropriate combination ofswitches (not shown) as is known in the art.

Atrial sensing circuits 244 and ventricular sensing circuits 246 mayalso be selectively coupled to the right atrial lead 104, coronary sinuslead 106, and the right ventricular lead 108, through the switch 226 fordetecting the presence of cardiac activity in each of the four chambersof the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR.SENSE) sensing circuits, 244 and 246, may include dedicated senseamplifiers, multiplexed amplifiers, or shared amplifiers. Switch 226determines the “sensing polarity” of the cardiac signal by selectivelyclosing the appropriate switches, as is also known in the art. In thisway, the clinician may program the sensing polarity independent of thestimulation polarity. The sensing circuits (e.g., 244 and 246) areoptionally capable of obtaining information indicative of tissuecapture.

Each sensing circuit 244 and 246 preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables the device 100 to deal effectively withthe difficult problem of sensing the low amplitude signalcharacteristics of atrial or ventricular fibrillation.

The outputs of the atrial and ventricular sensing circuits 244 and 246are connected to the microcontroller 220, which, in turn, is able totrigger or inhibit the atrial and ventricular pulse generators 222 and224, respectively, in a demand fashion in response to the absence orpresence of cardiac activity in the appropriate chambers of the heart.Furthermore, as described herein, the microcontroller 220 is alsocapable of analyzing information output from the sensing circuits 244and 246 and/or the data acquisition system 252 to determine or detectwhether and to what degree tissue capture has occurred and to program apulse, or pulses, in response to such determinations. The sensingcircuits 244 and 246, in turn, receive control signals over signal lines248 and 250 from the microcontroller 220 for purposes of controlling thegain, threshold, polarization charge removal circuitry (not shown), andthe timing of any blocking circuitry (not shown) coupled to the inputsof the sensing circuits, 244 and 246, as is known in the art.

For arrhythmia detection, the device 100 may utilize the atrial andventricular sensing circuits, 244 and 246, to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. Of course,other sensing circuits may be available depending on need and/or desire.In reference to arrhythmias, as used herein, “sensing” is reserved forthe noting of an electrical signal or obtaining data (information), and“detection” is the processing (analysis) of these sensed signals andnoting the presence of an arrhythmia or of a precursor or other factorthat may indicate a risk of or likelihood of an imminent onset of anarrhythmia.

The exemplary detector module 234, optionally uses timing intervalsbetween sensed events (e.g., P-waves, R-waves, and depolarizationsignals associated with fibrillation which are sometimes referred to as“F-waves” or “Fib-waves”) and to perform one or more comparisons to apredefined rate zone limit (i.e., bradycardia, normal, low rate VT, highrate VT, and fibrillation rate zones) and/or various othercharacteristics (e.g., sudden onset, stability, physiologic sensors, andmorphology, etc.) in order to determine the type of remedial therapy(e.g., anti-arrhythmia, etc.) that is desired or needed (e.g.,bradycardia pacing, anti-tachycardia pacing, cardioversion shocks ordefibrillation shocks, collectively referred to as “tiered therapy”).Similar rules can be applied to the atrial channel to determine if thereis an atrial tachyarrhythmia or atrial fibrillation with appropriateclassification and intervention. Such a module is optionally suitablefor performing various exemplary methods described herein. For example,such a module (e.g., the module 234, the module 239, etc.) optionallyallows for analyses related to action potentials (e.g., MAPs, T waves,etc.) and characteristics thereof (e.g., alternans, activation times,repolarization times, derivatives, etc.).

Cardiac signals are also applied to inputs of an analog-to-digital (A/D)data acquisition system 252. The data acquisition system 252 isconfigured to acquire intracardiac electrogram (IEGM) signals or otheraction potential signals, convert the raw analog data into a digitalsignal, and store the digital signals for processing and/or telemetrictransmission to an external device 254. The data acquisition system 252is coupled to the right atrial lead 104, the coronary sinus lead 106,the right ventricular lead 108 and/or the nerve stimulation lead throughthe switch 226 to sample cardiac signals across any pair of desiredelectrodes. As is described below, the IEGM signals are used by theischemia detection module 239 to detect myocardial ischemia.

Various exemplary mechanisms for signal acquisition are described hereinthat optionally include use of one or more analog-to-digital converter.Various exemplary mechanisms allow for adjustment of one or moreparameters associated with signal acquisition.

The microcontroller 220 is further coupled to a memory 260 by a suitabledata/address bus 262, wherein the programmable operating parameters usedby the microcontroller 220 are stored and modified, as required, inorder to customize the operation of the stimulation device 100 to suitthe needs of a particular patient. Such operating parameters define, forexample, pacing pulse amplitude, pulse duration, electrode polarity,rate, sensitivity, automatic features, arrhythmia detection criteria,and the amplitude, waveshape, number of pulses, and vector of eachshocking pulse to be delivered to the patient's heart 102 within eachrespective tier of therapy. One feature of the described embodiments isthe ability to sense and store a relatively large amount of data (e.g.,from the data acquisition system 252), which data may then be used forsubsequent analysis to guide the programming of the device.

Advantageously, the operating parameters of the implantable device 100may be non-invasively programmed into the memory 260 through a telemetrycircuit 264 in telemetric communication via communication link 266 withthe external device 254, such as a programmer, transtelephonictransceiver, or a diagnostic system analyzer. The microcontroller 220activates the telemetry circuit 264 with a control signal 268. Thetelemetry circuit 264 advantageously allows intracardiac electrograms(IEGM) and other information (e.g., status information relating to theoperation of the device 100, etc., as contained in the microcontroller220 or memory 260) to be sent to the external device 254 through anestablished communication link 266.

The stimulation device 100 can further include one or more physiologicsensors 270. For example, the device 100 may include a “rate-responsive”sensor that may provide, for example, information to aid in adjustmentof pacing stimulation rate according to the exercise state of thepatient. However, the one or more physiological sensors 270 may furtherbe used to detect changes in cardiac output (see, e.g., U.S. Pat. No.6,314,323, entitled “Heart stimulator determining cardiac output, bymeasuring the systolic pressure, for controlling the stimulation”, toEkwall, issued Nov. 6, 2001, which discusses a pressure sensor adaptedto sense pressure in a right ventricle and to generate an electricalpressure signal corresponding to the sensed pressure, an integratorsupplied with the pressure signal which integrates the pressure signalbetween a start time and a stop time to produce an integration resultthat corresponds to cardiac output), changes in the physiologicalcondition of the heart, or diurnal changes in activity (e.g., detectingsleep and wake states). Accordingly, the microcontroller 220 responds byadjusting the various pacing parameters (such as rate, AV Delay, V-VDelay, etc.) at which the atrial and ventricular pulse generators, 222and 224, generate stimulation pulses.

While shown as being included within the stimulation device 100, it isto be understood that one or more of the physiologic sensors 270 mayalso be external to the stimulation device 100, yet still be implantedwithin or carried by the patient. Examples of physiologic sensors thatmay be implemented in device 100 include known sensors that, forexample, sense respiration rate, pH of blood, ventricular gradient,cardiac output, preload, afterload, contractility, and so forth. Anothersensor that may be used is one that detects activity variance, whereinan activity sensor is monitored diurnally to detect the low variance inthe measurement corresponding to the sleep state. For a completedescription of the activity variance sensor, the reader is directed toU.S. Pat. No. 5,476,483 (Bornzin et. al), issued Dec. 19, 1995, whichpatent is hereby incorporated by reference.

The one or more physiological sensors 270 optionally include sensors fordetecting movement and minute ventilation in the patient. Signalsgenerated by a position sensor, a MV sensor, etc., may be passed to themicrocontroller 220 for analysis in determining whether to adjust thepacing rate, etc. The microcontroller 220 may monitor the signals forindications of the patient's position and activity status, such aswhether the patient is climbing upstairs or descending downstairs orwhether the patient is sitting up after lying down.

The stimulation device 100 additionally includes a battery 276 thatprovides operating power to all of the circuits shown in FIG. 2. For thestimulation device 100, which employs shocking therapy, the battery 276is capable of operating at low current drains for long periods of time(e.g., preferably less than 10 μA), and is capable of providinghigh-current pulses (for capacitor charging) when the patient requires ashock pulse (e.g., preferably, in excess of 2 A, at voltages above 200V, for periods of 10 seconds or more). The battery 276 also desirablyhas a predictable discharge characteristic so that elective replacementtime can be detected.

The stimulation device 100 can further include magnet detectioncircuitry (not shown), coupled to the microcontroller 220, to detectwhen a magnet is placed over the stimulation device 100. A magnet may beused by a clinician to perform various test functions of the stimulationdevice 100 and/or to signal the microcontroller 220 that the externalprogrammer 254 is in place to receive or transmit data to themicrocontroller 220 through the telemetry circuits 264.

The stimulation device 100 further includes an impedance measuringcircuit 278 that is enabled by the microcontroller 220 via a controlsignal 280. Exemplary uses for an impedance measuring circuit 278include, but are not limited to, lead impedance surveillance during theacute and chronic phases for proper lead positioning or dislodgement;detecting operable electrodes and automatically switching to an operablepair if dislodgement occurs; measuring respiration or minuteventilation; measuring thoracic impedance for determining shockthresholds; detecting when the device has been implanted; measuringstroke volume; and detecting the opening of heart valves, etc. Theimpedance measuring circuit 278 is advantageously coupled to the switch226 so that any desired electrode may be used. Impedance measurementsfor unipolar (electrode to case electrode), bipolar or multipolarelectrode configurations may be possible depending on features (e.g.,number of leads, switching, number of electrodes, etc). Impedance may beintracardiac, intrathoracic or other.

In the case where the stimulation device 100 is intended to operate asan implantable cardioverter/defibrillator (ICD) device, it detects theoccurrence of an arrhythmia, and automatically applies an appropriatetherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, the microcontroller 220 further controls a shocking circuit282 by way of a control signal 284. The shocking circuit 282 generatesshocking pulses of low (e.g., up to 0.5 J), moderate (e.g., 0.5 J to 10J), or high energy (e.g., 11 J to 40 J), as controlled by themicrocontroller 220. Such shocking pulses are applied to the patient'sheart 102 through at least two shocking electrodes, and as shown in thisembodiment, selected from the left atrial coil electrode 126, the RVcoil electrode 132, and/or the SVC coil electrode 134. As noted above,the housing 200 may act as an active electrode in combination with theRV electrode 132, or as part of a split electrical vector using the SVCcoil electrode 134 or the left atrial coil electrode 126 (i.e., usingthe RV electrode as a common electrode).

Cardioversion level shocks are generally considered to be of low tomoderate energy level (so as to minimize pain felt by the patient),and/or synchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (e.g., corresponding to thresholds in the range ofapproximately 5 J to 40 J), delivered asynchronously (since R-waves maybe too disorganized), and pertaining exclusively to the treatment offibrillation. Accordingly, the microcontroller 220 is capable ofcontrolling the synchronous or asynchronous delivery of the shockingpulses.

First Definition of ST Segment Amplitude Measurement

FIG. 3 is a schematic of an IEGM signal for a patient suffering frommyocardial ischemia, and shows ST segment elevation resulting from theischemia. In one illustrative embodiment, the interval between times t3and t4 defines an early section of the ST segment which will be used todetermine ST segment elevation, which the remainder of the ST segment isignored. In that embodiment, the electrogram amplitude is measured inthe interval between times t3 and t4 to monitor for ischemia. In oneembodiment, t3 and t4 are preferably selected in such a way that noportion of the T wave will be included. The exemplary values of t3 andt4 are 50 msec and 100 msec after the Q wave, respectively. The windowcould also be started some amount of time following detection of the Rwave (e.g., following the onset of the R wave or following the R wavepeak), following the detection of the onset of the QRS complex, or evenfollowing the end of the QRS complex.

As shown in FIG. 3, the pre-P wave interval between t1 and t2 islabeled, and in certain embodiments will be used as a reference value incalculating the ST segment elevation. Exemplary values of t1 and t2 are20 msec and 10 msec before the P wave, respectively. It will also beapparent to those skilled in the art that the reference value may be theperiod between the P-wave and the QRS complex, or a historical baselinemay be used as the reference value.

Effect of Ischemia on ST Segment Amplitude Measurement

QRST morphology changes for intrinsic rhythms due to an evolvingischemic condition are shown in FIG. 4. FIG. 4 shows 7 minutes worth ofQRST complexes superimposed on each other. The recordings were made froma unipolar right ventricular tip (RVT) electrode in a canine. Bandwidthwas 0.05-250 Hz. The ischemic condition was induced by occluding thedistal branch of the left anterior descending (LAD) coronary artery.While the recordings were made from a unipolar RVT electrode, it will beapparent to those skilled in the art that many different electrodeconfigurations may be used to make the recordings, including a unipolarright ventricular ring (RVR) configuration, bipolar configurationsbetween the RVT and RVR electrodes, and the like.

As shown in FIG. 4, a first tracing 402 comes from the first minute ofnon-ischemic baseline condition. At the end of the first minute ofrecording, the balloon was inflated. A second tracing 404 is from thefirst minute post occlusion. Third tracing 406 is from 1-2 minutes postocclusion, fourth tracing 408 from 2-3 minutes post occlusion, fifthtracing 410 from 3-4 minutes post occlusion, and sixth tracing 412 from4-5 minutes post occlusion. Five minutes after the balloon was inflated,it was deflated. A seventh tracing 414 comes from the first minute afterdeflating the balloon. The changes in ST elevations due to the inducedischemic condition are clearly visible in FIG. 4. The tracings may alsobe baseline-adjusted by subtracting the pre-P values (discussed earlier)from each sample.

The average of EGM amplitude sample values during the period between 50msec and 100 msec after the Q wave is termed ‘ST1’. The time intervalover which ST1 is calculated is depicted in FIG. 4 as between 300 and350 millseconds (i.e., between approximately 50 and 100 millisecondsfrom the onset of the Q wave). The value of ST1 over the course of aninduced ischemic episode (approximately 7 minutes) is shown in FIG. 5.The first region 502 represents non-ischemic baseline EGM level. Thesecond region 504 represents 1 minute into the occlusion. The thirdregion 506 is for 1-2 minute into occlusion, the fourth region 508 for2-3 minute into occlusion, the fifth region 510 for 3-4 minute intoocclusion, the sixth region 512 for 4-5 minute into occlusion andseventh region 514 is after the removal of occlusion by deflating theballoon. ST1 begins to change upon occlusion of the artery (as shown bythe second region 504) and the change becomes larger the longer theocclusion remains, reaching the maximum at 5 minutes (sixth region 512).ST1 promptly returns to baseline upon removal of occlusion (seventhregion 514).

A similar trend appears in FIG. 6 which shows the change in average EGMlevel for the interval between 100 msec and 150 msec after the Q-wave,termed ‘ST2’ in FIG. 4. These times are also shown as t4 and t5respectively in FIG. 3. In at least certain embodiments, is notdesirable to extend t5 beyond 150 msec after the Q-wave since this mayresult in the window capturing part of the T wave, as is shown in FIG.3.

Thus, as shown in FIGS. 5 and 6, the IEGM level change within the earlyST segment(s) is a good indication of an ischemic condition.Furthermore, the early ST segment(s) ignore any T-wave signal influenceswhich could adversely affect the measurement.

Referring now to FIG. 7, one embodiment of a method for detectingischemia will be described. At step 700, ventricular activity isdetected using one or more electrode pairs as described above. At step702, a detection window is opened for a predetermined time after theventricular activity is detected. In one embodiment, the window isopened for about 50 milliseconds following the onset of ventricularactivity. It will be understood that the window may be opened for apredetermined time following detection of the R-wave peak, or followingthe end of the QRS complex, or any other suitable event. In addition,the detection window may correspond to the ST1 segment of FIG. 4, theST2 segment, or any other relatively early portion of the overall STsegment.

At step 704, the portion of the IEGM signal within the window is sensed,and the amplitude of the IEGM signal is determined. As described above,the amplitude may be compared relative to a baseline reference, or tothe PQ segment as the reference value. The amplitude may be the maximumvalue within the window, or an average of the values sensed within thewindow. Preferably, the pre-P value is determined and used as thereference value to determine the ST segment value within the window.Moreover, as described above, the IEGM signal could be ensemble averagedover a number of cycles, or averaged in some other manner to attenuatenoise and other non-cardiac signals.

At step 706, the ST segment value is compared to a threshold or otherstored value to determine if the ST segment value indicates myocardialischemia. In one embodiment, a threshold value is stored in theimplanted device 100, and the ST segment value is compared to thethreshold value. If the ST segment value exceeds the threshold value,then ischemia is detected at query block 708. In another embodiment, acurrent ST segment value is compared to a previously stored ST segmentvalue, and if the current value exceeds the previously stored value bymore than a predetermined amount, then ischemia is detected.

If ischemia is detected at block 708, operation optionally proceeds tostep 710, and some responsive action is preferably taken. For example,the implanted device 100 may change one or more operating parameters inresponse to detecting ischemia, such as lowering the base pacing rate orotherwise attempting to lower the heart rate (e.g., through neurologicalstimulation). Alternatively, the implanted device 100 may generate awarning signal to warn the patient of the ischemic condition. Theimplanted device 100 may also telemeter data and/or a warning to anexternal device, such as a bedside monitor or other external device. Inanother embodiment, the implanted device 100 may simply record datacorresponding with the detection of ischemia.

General Definition of STn Segment Amplitude Measurement(s)

It will be understood by those skilled in the art that variousmethodologies may be utilized to determine ST segment values. Thefollowing are a few examples of such methodologies.

In one illustrative embodiment, the average ST segment amplitudemeasurements are made over a plurality of heart cycles. Generally, thesemeasurements will be hereinafter termed STn, where the exemplary casesn=1 and n=2 are defined above. A set of measurements may be made (e.g.STn where n=1 to 5). These measurements may include portions of the IEGMduring and/or shortly after onset of the T-wave. This scheme isillustrated in FIG. 4 with five segments separated by vertical dashedlines (only two of which are labeled as ST1 and ST2, the remainingsegments would be labeled ST3, ST4, and ST5).

STn Measurement(s) Made on Ensemble Averaged PQRST Complex

To support ischemia detection, in one embodiment the STn values may bemeasured periodically on an ensemble-average of several (e.g. 8-16)consecutive or closely occurring QRST complexes (e.g., within a fewminutes of each other). Ensemble averaging has benefit in that signalcomponents such as noise and respiration artifacts uncorrelated with thecardiac cycle are attenuated. Paced and sensed complexes, if both areoccurring, will contribute to separate averaged waveforms. In oneembodiment, only sensed complexes are used to determine ST segmentvalues.

STn Measurement(s) Made on Several PQRST Complexes and Statistics Kept

Alternately, the STn values may be measured periodically for each ofseveral individual consecutive or approximately consecutive complexesand statistics calculated on the several measurements. Statisticalparameters to be estimated may include the mean and the variance, or anyother suitable parameter to determine an average ST segment value forpurposes of monitoring for ischemia.

Measurement of Absolute STn Amplitude vs. Measurement of ΔSTn AmplitudeChange Relative to Historical Baseline and Comparison to a Threshold.

ST segment elevation is typically approximately equal to the isoelectricbaseline (which in one illustrative embodiment is the pre-P valuediscussed above) in the absence of a pathological condition. Therefore,STn may be taken as an absolute measurement at any time and ischemiadetected if STn exceeds a threshold.

As seen in FIGS. 5 and 6, however, baseline (nonischemic) STn values arenot always exactly zero. A nonzero baseline value may arise due to thefrequency bandlimiting of asymmetrical QRS complexes. At short AVdelays, it may be due to far-field atrial repolarization. It is expectedthat the baseline may also change slightly over time. It may be affectedindirectly by changes in QRS morphology. It may also be affecteddirectly by electrolyte imbalances, such as hypokalemia, which may occursecondary to insulin-induced hypoglycemia. STn changes due to acuteischemia are expected to evolve rapidly (e.g. over the course of aminute or two), where changes due to systemic influences (e.g.hypokalemia) are expected to evolve more slowly.

Therefore, in at least some embodiments it may be desirable to compareSTn to one or more historical values on a periodic basis. A change inSTn relative to a historical baseline value is hereinafter termed ΔSTn.Ischemia may be detected if ΔSTn exceeds a threshold.

In another embodiment, the implanted device 100 may compute a short-termaverage value (e.g., taken over a plurality of cycles within the lastfew minutes) as well as a long-term average value (e.g., taken over aperiod of weeks, months, etc.). In this embodiment, if a short-termaverage value exceeds a long-term average value by more than a thresholdamount (or alternately by more than a percentage of the long-termaverage value), then ischemia is indicated. The long-term average valueaccounts for slowly evolving shifts in the ST segment.

Frequency of STn measurement and threshold comparison

The definition of “historical baseline” above (not to be confused withisoelectric baseline) and the interval at which STn and/or ΔSTn aremeasured may appropriately depend on the application. For example, for along-term ischemia burden trend metric, detection might be donerelatively infrequently—just frequently enough that it is likely that adetection would occur during an ischemic episode of average length. Inthis application, STn and/or ΔSTn might be measured every ten minuteswith historical baseline values for ΔSTn determined at a single point intime (e.g. at implant or at the command of a clinician) or to thelong-term average value determined over a relatively long period of time(e.g. over the previous week).

In the context of acute ischemia event detection, especially where somekind of action might be taken in response, STn and/or ΔSTn might bemeasured relatively often (e.g. every 30 seconds). In this context, thehistorical baseline might be more appropriately determined from arelatively recent history (e.g. a moving average of values measured overthe previous hour). Acute myocardial ischemia would be indicated in thatembodiment if STn and/or ΔSTn measurements exceed correspondingthresholds.

Thus, it will be apparent that the implanted device 100 may store aplurality of thresholds and may monitor for ischemia using a pluralityof different detection schemes, some of which being described above.

Criteria for Ischemia Detection

In one embodiment, implanted device 100 might detect ischemia based on asingle STn or ΔSTn measurement that exceeds a corresponding threshold.It might be required that several (e.g. 3) consecutive measurementsexceed threshold. It might be required that the rate of measurementsexceeding threshold exceed a second threshold, e.g. at least 3 of 5consecutive measurements. Alternately, it might be required that ameasure of statistical significance (e.g. T-value) between a set ofhistorical baseline measurements and subsequent set of measurementsexceed a threshold.

The T-value is defined as:

Tvalue=(|mean1−mean2|)/sqrt(std12+std22)

where mean1 and mean2 are the means of the set of historical baselinemeasurements a set of recent measurements respectively; and std12 andstd22 are the variances of the measurements in the historical baselineset and the set of recent measurements, respectively.

variance=ΣN(sample(n)−mean)2/N

An exemplary criteria for ischemia detection is Tvalue>2.

Treat Sensed and Paced Complexes Separately

STn and/or ΔSTn measurements may be made on intrinsic or pacedcomplexes, but paced and intrinsic measurements should not be combinedand should be evaluated separately. In case of paced complexes, the t3value (i.e., when the detection window opens) should be greater than t3in intrinsic complexes since paced complexes tend to have longer QRSdurations. Thus, while in one embodiment the t3 value may be 50milliseconds from detection of the QRS complex for intrinsic complexes,it might be 80 or even 100 milliseconds for paced complexes.

If an intrinsic complex is determined to be the result of a PVC (e.g.,through morphology, timing analysis, etc), that complex should not beincluded in the ST segment measurements.

Adjustment of Measurement for Rate

It may be desirable that the end time (e.g. t4 in FIG. 3) of the segmentadapt to heart rate. This is because the QT interval is expected to varywith heart rate, and as described in detail above it is desirable to endthe detection window (e.g., ST1, ST2, etc) before the start of theT-wave. This may be accomplished by application of Bazette's equation toestimate the amount of QT shortening at the current rate, and to reducet4 accordingly.

In another embodiment, if the start and end times of ST1 are correctlychosen, adjustment for rate may not be necessary.

There is an upper limit of rate above which measurements should beconsidered invalid. This limit is approximately 120 bpm, where theentire ST segment duration is expected to be <70 ms.

Pattern Recognition with Multiple Measurements

It may prove desirable to combine measurements from a set ofmeasurements (e.g. ST1-ST5) in order to improve sensitivity and/orspecificity. It may be that such a set of measurements will reveal apattern unique to ischemia and different from patterns which might beproduced by other confounding influences. An example of such a patternmight be an increase in ST1, ST2 and ST3 with ST5 remaining constant ordecreasing and with the increase in ST3>increase in ST2>increase in ST1.

For consistency of the above multi-dimensional measurement consideringrate variations, it may prove desirable to adjust the duration of allthe segments together such that each segment covers a consistentproportion of the overall ST segment as it varies with rate.

It may be that variations in such a pattern might indicate roughly thelocation of occlusion. Discernment of the existence and location ofocclusion may be enhanced by applying these techniques over multiplesensing vectors which may be provided by multiple leads.

Many forms of pattern classifiers which classify multi-dimensionalmeasurements are discussed in the literature may be applicable here.These include classifiers based on Bayesian minimum error, minimumdistance and decision trees.

Record of Burden Metric

An implanted device preferably stores a record in memory of theoccurrence of ischemic episodes. In one embodiment the ischemic episodedata may be processed to define a burden metric, including storing andupdating the metric, and displaying it to the user in a useful format.

The burden metric may simply be the ratio of periodic measurements forwhich ischemia was indicted (X) to the total number of periodicmeasurements (Y). This may be presented as X of Y or simply Z=X/Y.

The burden metric may include measures of certainty and/or severity ofischemia. This could lead to a multi-dimensional burden metric.

In one embodiment for example, the degree by which a feature exceeds itsthreshold for ischemia detection may mapped to a severity/likelihoodindex which can take values from 1-5 where 1 indicates the threshold fordetection was barely exceeded and 5 indicates it was exceeded by atleast 100%. Then the burden metric above would keep a count ofdetections of each severity level (e.g. Xn/Y where n=1-5).

If more than one parameter is used for detection, X may be2-dimensional, e. g. Xn,m where X is a count, n is a severity level andm indicates an enumerated feature. An additional dimension to X mayinclude the value of the activity sensor at the time of measurement.

In the above examples, Y may represent all the measurements made sincethe last follow-up. Preferably, the metric will be recorded periodicallyby the device so that changes over time can be observed. Ideally, Xwould be stored for every measurement. More X/Y would be storedperiodically, e.g. every day or every week.

The ischemia burden record is preferably presented to the user as agraph of burden vs. time, analogous to the way atrial tachycardia andatrial fibrillation burden is presented to physicians. Multipledimensions of X may be presented as separate traces on the graph.

Finally, a measure of correlation between activity sensor output andischemia burden (or likelihood/severity of ischemia) would be anotheruseful metric. This could be calculated for each point where theischemia metric is recorded (e.g. daily or weekly), for the entirehistory in memory, or for both.

Example Embodiments

FIG. 8 depicts a process comprising many of the above concepts. When itis time to measure STn, the device begins at 805 to buffer the IEGM fora duration equal to or greater than the time from the end of theprevious T-wave to the end of the most recent T-wave, so as to includepre-P isoelectric baseline for the most recent PQRST complex.

Then the process waits at 810 for an appropriate sensed or pacedventricular event. PVCs or events occurring at too high a rate may beexcluded as inappropriate.

The following steps are executed on the electrogram signal buffered inmemory. In the case where V-pacing is being encouraged or forced (e.g.for ventricular resynchronization therapy,) steps 815-840 may beappropriately skipped for sensed events. In the case where inhibition ofventricular pacing is being encouraged or forced, steps 815-840 may beskipped for paced measurements.

In 815 the pre-P baseline is optionally measured. The t1 and t2 valuesin FIG. 3 may be determined relative to R-sense or V-pace or relative toP-sense or A-pace. Preferably, the t2 value precedes the start of theP-wave.

In 820, the start and end time(s) of the interval(s) STn are utilized tomeasure ST segment amplitudes. Because paced QRS complexes are typicallylonger in duration than intrinsic QRS complexes, start time of STn (e.g.t3 in FIG. 1) may be longer for paced than for sensed complexes. Alsobecause QT depends on rate, the end time of the STn interval (e.g. t4 inFIG. 1) may need to be shortened at higher rates. If measurements arebeing made for multiple segments, the start and end times of all of them(e.g., ST1, ST2, etc.) may be adjusted.

In step 825 the measurement of average amplitude is made (if applicable)during the applicable interval(s) STn within the ST segment, e.g.between t3 and t4 in FIG. 1.

In step 830, the measurement made in step 825 is preferably referencedto a baseline value by subtracting the pre-P measurement made in step815. For step 830, it is important to note that if measurements arebeing made on both paced and sensed complexes, they be storedseparately.

Steps 835 and 840 calculate mean and variance respectively for multiplemeasurements of STn elevation made in multiple passes through steps815-830. These steps may be done for each pass through steps 815-830 asshown. In one embodiment, moving average techniques may be used toapproximate mean and variance. If statistics are not required in step845, steps 835 and 840 may be carried out once after step 845.

In step 845 it is decided if sufficient paced and sensed measurementshave been made. The number of measurements may be a fixed number, e.g. 8paced events and 8 sensed events. The decision might also involve anevaluation of statistical significance. For example, sufficient pacedmeasurements may have been made if the T value is <2 or if 8measurements have been made. In the case where V-pacing is beingencouraged or forced (e.g. for ventricular resynchronization therapy,)zero sensed events may be enough. In the case where ventricular sensedmeasurements are preferred (e.g. if ventricular pacing is temporarilybeing avoided to improve perfusion during an ischemic episode,) zeropaced measurements may be enough.

FIG. 9 depicts a process which is a variation on the process in FIG. 8.

In step 915, several consecutive or nearly consecutive electrogramcomplexes are ensemble averaged to produce an averaged pre-P throughpost-T waveform segment in which non-cardiac signal components such asnoise and respiration artifact are attenuated. Paced and sensedcomplexes, if both are occurring, will contribute to separate averagedwaveforms.

Step 920 is analogous to step 845, except that after enough complexeshave been averaged, the process proceeds to make a measurement of theelectrogram feature(s) of interest. Paced and sensed averaged complexesare handled independently.

Steps 925-940 are analogous to steps 815-830.

FIG. 10 shows one illustrative embodiment of a method for monitoringischemia burden.

At step 1005, an initial historical baseline is preferably established.This would occur at some predetermined time (e.g., at implant) or per acommand from a programmer. This step is not needed if only absolutefeature measurements are to be made. Historical baseline information maybe stored in the form(s) discussed above, e.g. in the form of featuremeasurement mean(s) and optionally variance(s).

At step 1010, the process waits until it is time to make a measurement.Appropriate measurement intervals for ischemia burden monitoring rangefrom every 30 seconds to every day. An interval in the range from 1-10minutes is preferred. Instead of or in addition to a regular intervalfor measurements, measurements may be set to occur at specific times ofday and/or when the patient has been at rest (as indicated by anactivity sensor) for a predetermined time.

At step 1015, pacing therapy is optionally adjusted to provide favorableconditions for measurement. For example, AV hysteresis may be envoked toencourage V-pacing or inhibition if primarily paced or sensedmeasurements are desired. In a ventricular resynchronization therapydevice, V-V timing may be adjusted. The pacing rate may be slowed to atarget rate if it is currently elevated, e.g. due to rate response foractivity. The pacing rate may be slightly increased to a target ratetemporarily to provoke ischemia in case myocardial oxygen demand is onthe verge of exceeding supply.

Step 1020 optionally confirms that favorable conditions for measurementexist. If they do not, e.g. if the intrinsic rate is too fast, ameasurement is not made at this time. Rather the existence ofunfavorable conditions is optionally logged at step 1040, and theprocess returns to step 1010. The time to the next measurement may beoptionally advanced.

At step 1024, the parameter(s) of interest is/are measured, e.g. STnaccording to the processes in FIG. 8 or FIG. 9. It should be noted thatany number of parameters for ischemia detection may be used here. Theseinclude, among others, QT max, QT end, QRS morphology, PR segmentamplitude.

At step 1030, it is determined whether or not the measurement indicatesischemia is present. This determination may be made per any of themethods discussed above, e.g. comparing the absolute measurement(s) to athreshold, comparing the recent measurement to a historical baseline, orevaluating a pattern classifier for multiple parameters. Any of thesemethods may also involve evaluation of statistical significance, asdiscussed above.

If ischemia is not indicated at step 1030, historical baselines areoptionally updated at step 1045. As discussed above, historical baselineinformation may be updated by keeping one or more moving averages ofparameter mean(s) and variance(s). For example, a fast average (e.g.over the last hour), a slow average (e.g. over the last day or longer)or both may be updated.

If ischemia is detected at step 1030, a burden metric is preferablycalculated and the record of burden is updated as discussed above. Inaddition, the implanted device 100 may take appropriate action, such asgenerating a warning signal, telemetering out data to an externaldevice, and the like.

1. A system for detecting ischemia comprising: at least one leadconfigured for placement within a patient, the at least one leadcomprising a sensor operative to sense ventricular activity and togenerate a corresponding signal; and an implantable medical deviceconfigured for connection to the at least one lead, the implantablemedical device comprising circuitry operative to receive signals fromthe sensor corresponding to ventricular activity, to open a window apredetermined time after sensing the ventricular activity, wherein thewindow is shorter than the ST segment, the circuitry being furtheroperative to determine an amplitude value within the window, and toprocess the amplitude value to detect ischemia.
 2. The system of claim 1wherein the circuitry is operative to open the window between 50 and 100milliseconds after the onset of a Q wave.
 3. The system of claim 1wherein the circuitry is operative to open the window between 100 and150 milliseconds after the onset of a Q wave.
 4. The system of claim 1wherein the circuitry is operative to compare the amplitude value to athreshold to detect ischemia.
 5. The system of claim 4 wherein thethreshold is a historical baseline value.
 6. The system of claim 5wherein the threshold is a long-term average value.
 7. The system ofclaim 1 wherein the circuitry is operative to determine the amplitudevalue by measuring the amplitude value relative to an isoelectricbaseline.
 8. The system of claim 7 wherein the isoelectric baseline ismeasured during an interval between a T-wave and subsequent P-wave. 9.The system of claim 1 wherein the circuitry is operative to determinethe amplitude value by taking a plurality of measurements anddetermining an average value.
 10. The system of claim 9 wherein theplurality of measurements are taken over multiple cycles.
 11. The systemof claim 1 wherein the circuitry is operative to open a window byopening the window at a first time if the ventricular activity isintrinsic, and at a second time if the ventricular activity is paced.12. The system of claim 1 and wherein the circuitry is further operativeto compute an ischemia burden value based on the processing anddetecting of ischemia.